This application will support and renew the Medical Scientist Training Program (MSTP) at Stanford University School of Medicine. In 42 years of continuous NIH funding, 248 trainees have graduated from this program, many of whom have become leaders in their fields of academic medicine and biomedical research. Our program provides a superb environment and unique advantages for fulfilling our mission to train pioneering physician-scientists dedicated to a lifetime of biomedical discovery that improves human health through innovation. Dual degree pre-doctoral training in the Stanford MSTP benefits from many established strengths, including (1) a University campus with adjacent Schools of Medicine, Engineering, and Humanities & Sciences whose setting and facilities encourage interdisciplinary investigations; (2) a world-class faculty devoted to biomedical research and mentoring; (3) a diverse, accomplished medical student body selected from a highly qualified applicant pool and attracted by a curriculum whose centerpiece is the Scholarly Concentration Program, and supported by institutional resources including the new Knowledge and Learning Center; and (4) clinical training programs in a diversity of settings, including tertiary care, county hospital, Veterans Administration Hospital, HMO and community outpatient clinics. These and other strengths have durably produced successful outcomes in our trainees, based on several metrics used to compare MD- PhD programs nationally, including low attrition, time to degree conferral, publication record, and high retention of graduates in biomedical research careers. This proposal also describes important changes in the Stanford program structure that are highly responsive to concerns raised in the last review of our MSTP. These program enhancements include a significantly increased level of institutional support, reflected in increased staffing and faculty effort to direct the MSTP; increased financial support for student training by the School of Medicine; periodic internal and external program evaluation; creation and implementation of MSTP-specific innovative courses and teaching programs; improved mentoring and monitoring mechanisms for students throughout their training; increased faculty participation; and enhanced vertical integration among trainees. Together, the increased institutional support, increased effort by School of Medicine faculty and leadership, dedicated program enhancements, and integration of clinical and graduate training have changed, expanded and improved the Stanford MSTP. The number of dual-degree students trained and supported by the MSTP more than quadruples the number of trainee positions provided by the NIGMS T32. Support through this proposal, leveraged with School of Medicine resources, will support continuing innovation in training physician scientists at Stanford devoted to improving human health through a lifetime of biomedical research.